While much work has been published on the dynamics of T cells-changes in representation of CD4 and CD8 cells-during HIV disease progression and treatment (HAART), much less is known about the changes in the functional subsets of T cells. Indeed, virtually nothing is known about the changes in the mucosal T cells-those cells residing in the gut or other peripheral sites (but can traffic via the blood and are found at low frequencies there). We are investigating the interrelationship of the mucosal and central immune systems, using our unique 12-color flow cytometric technology to derive as much information as possible from each animal. We are evaluating the functional status of the dozens of unique T cell subsets in blood, lymphoid organs, and mucosal sites during SIV disease and subsequent therapeutic regimens. We are also comparing these parameters in animals that have undergone vaccine regimens, to understand whether or not the vaccines have altered the specific immune response to the virus and the impact of such changes on clinical outcome.